Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Gastroenterology. 2022 Dec;163(6):1522-1530.e5. doi: 10.1053/j.gastro.2022.08.020. Epub 2022 Aug 13.
BACKGROUND & AIMS: Interval colorectal cancers (CRCs), cancers diagnosed after a screening/surveillance examination in which no cancer is detected, and before the date of next recommended examination, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison with screen detected CRCs.
We included 1175 CRCs documented in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and 3661 CRCs in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Multivariable Cox models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of death risk. Whole exome sequencing was conducted in 147 PLCO cases and 796 NHS/HPFS cases.
A total of 619 deaths (312 CRC-specific) and 2404 deaths (1904 CRC-specific) were confirmed during follow-up of PLCO and NHS/HPFS, respectively. Compared with screen detected CRCs, interval CRCs had a multivariate-adjusted HR (95% CI) of 1.47 (1.21-1.78) for CRC-specific mortality and 1.27 (1.09-1.47) for overall mortality (meta-analysis combining all 3 cohorts). However, we did not observe significant differences in mutational features between interval and screen detected CRCs (false discovery rate adjusted P > .05).
Interval CRCs had a significantly increased risk of death compared with screen detected CRCs that were not explained by established clinical prognostic factors, including stage at diagnosis. The survival disadvantage of interval CRCs did not appear to be explained by differences in the genomic landscape of tumors characterized by whole exome sequencing.
间期结直肠癌（CRC）是指在筛查/监测检查中未发现癌症，且在下一次推荐检查日期之前诊断出的癌症，这反映了 CRC 检测和预防方面前所未有的挑战。为了更好地了解这种特征不佳的 CRC 变异，我们比较了间期 CRC 和筛查发现的 CRC 的临床和突变特征。
我们纳入了前列腺癌、肺癌、结直肠癌和卵巢癌（PLCO）筛查试验中记录的 1175 例 CRC 和护士健康研究（NHS）和健康专业人员随访研究（HPFS）中的 3661 例 CRC。多变量 Cox 模型用于估计死亡风险的风险比（HR）和 95%置信区间（CI）。对 147 例 PLCO 病例和 796 例 NHS/HPFS 病例进行了全外显子组测序。
在 PLCO 和 NHS/HPFS 的随访中，共确认了 619 例死亡（312 例 CRC 特异性）和 2404 例死亡（1904 例 CRC 特异性）。与筛查发现的 CRC 相比，间期 CRC 的 CRC 特异性死亡率的多变量调整 HR（95%CI）为 1.47（1.21-1.78），总死亡率为 1.27（1.09-1.47）（合并所有 3 个队列的荟萃分析）。然而，我们没有观察到间期和筛查发现的 CRC 之间在突变特征上有显著差异（假发现率调整 P>.05）。
与筛查发现的 CRC 相比，间期 CRC 的死亡风险显著增加，这不能用既定的临床预后因素来解释，包括诊断时的分期。全外显子组测序所描述的肿瘤基因组景观特征差异似乎并不能解释间期 CRC 的生存劣势。
